全文获取类型
收费全文 | 1458篇 |
免费 | 120篇 |
国内免费 | 9篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 64篇 |
妇产科学 | 30篇 |
基础医学 | 205篇 |
口腔科学 | 27篇 |
临床医学 | 147篇 |
内科学 | 349篇 |
皮肤病学 | 41篇 |
神经病学 | 65篇 |
特种医学 | 113篇 |
外科学 | 189篇 |
综合类 | 39篇 |
预防医学 | 78篇 |
眼科学 | 10篇 |
药学 | 135篇 |
中国医学 | 7篇 |
肿瘤学 | 83篇 |
出版年
2022年 | 11篇 |
2021年 | 13篇 |
2018年 | 12篇 |
2017年 | 8篇 |
2016年 | 13篇 |
2015年 | 19篇 |
2014年 | 31篇 |
2013年 | 32篇 |
2012年 | 31篇 |
2011年 | 45篇 |
2010年 | 41篇 |
2009年 | 39篇 |
2008年 | 49篇 |
2007年 | 58篇 |
2006年 | 50篇 |
2005年 | 33篇 |
2004年 | 55篇 |
2003年 | 42篇 |
2002年 | 39篇 |
2001年 | 51篇 |
2000年 | 38篇 |
1999年 | 41篇 |
1998年 | 35篇 |
1997年 | 37篇 |
1996年 | 44篇 |
1995年 | 35篇 |
1994年 | 26篇 |
1993年 | 26篇 |
1992年 | 29篇 |
1991年 | 28篇 |
1990年 | 40篇 |
1989年 | 35篇 |
1988年 | 43篇 |
1987年 | 34篇 |
1986年 | 42篇 |
1985年 | 45篇 |
1984年 | 36篇 |
1983年 | 39篇 |
1982年 | 20篇 |
1981年 | 25篇 |
1980年 | 19篇 |
1979年 | 21篇 |
1978年 | 29篇 |
1977年 | 22篇 |
1976年 | 16篇 |
1975年 | 17篇 |
1974年 | 13篇 |
1973年 | 12篇 |
1972年 | 15篇 |
1970年 | 11篇 |
排序方式: 共有1587条查询结果,搜索用时 0 毫秒
1.
Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine 总被引:2,自引:0,他引:2
Kupffer cells are activated by calcium and release a variety of toxic mediators, including proteases. The purpose of these studies, therefore, was to determine if protease inhibitors and a calcium channel blocker could increase survival time in the rat model of orthotopic liver transplantation. Survival for 30 days was greater than 90% in this model when livers were stored for 1 hr in Ringer's solution (survival conditions)--however, grafts stored for 4 hr in Euro-Collins solution or 8 hr in University of Wisconsin (UW) solution survived postoperatively only 1.2 and 0.7 days, respectively (nonsurvival conditions). When livers were stored for 4 hr in Euro-Collins containing a cocktail of protease inhibitors (leupeptin, pepstatin A, phenylmethylsulfonyl fluoride, 20 ng/ml each; diisopropyl fluorophosphate, 100 microM) and subsequently transplanted, however, survival time was increased significantly to 11.5 days. Inclusion of a calcium channel blocker, nisoldipine (1.4 microM), in the protease inhibitor cocktail increased survival time to 23 days. Actually, nisoldipine alone increased survival time to 25 days. Nisoldipine alone also increased survival time in livers stored for 8 or 16 hr in UW solution to between 15 and 20 days. Serum transaminase levels reached peak values greater than 2400 U/L one day postoperatively in the nonsurvival groups, and liver injury assessed histologically was apparent. Under these conditions, pulmonary infiltration of inflammatory cells was observed in about 60% of the lungs examined and was associated with massive bleeding. Inclusion of the protease cocktail, nisoldipine, or both in the storage solutions decreased maximal SGOT levels and injury to both liver and lung significantly by about 50% postoperatively. Nisoldipine also decreased phagocytosis of carbon particles by the perfused liver 2- to 3-fold following storage under nonsurvival conditions (half-maximal effect = 0.3-0.4 microM nisoldipine). Moreover, nisoldipine improved hepatic microcirculation. It accelerated blood flow into the liver, as indexed by hemoglobin reflectance from the liver surface. These data support the hypothesis that Kupffer cells are activated early in the sequence of events that causes graft failure leading to endothelial cell-mediated alterations in the microcirculation. This work demonstrates clearly that dihydropyridine-type calcium channel blockers such as nisoldipine may be clinically useful in storage solutions for liver prior to transplantation. 相似文献
2.
L. Ostrosky-Zeichner C. Sable J. Sobel B. D. Alexander G. Donowitz V. Kan C. A. Kauffman D. Kett R. A. Larsen V. Morrison M. Nucci P. G. Pappas M. E. Bradley S. Major L. Zimmer D. Wallace W. E. Dismukes J. H. Rex 《European journal of clinical microbiology & infectious diseases》2007,26(4):271-276
The study presented here was performed in order to create a rule that identifies subjects at high risk for invasive candidiasis
in the intensive care setting. Retrospective review and statistical modelling were carried out on 2,890 patients who stayed
at least 4 days in nine hospitals in the USA and Brazil; the overall incidence of invasive candidiasis in this group was 3%
(88 cases). The best performing rule was as follows: Any systemic antibiotic (days 1–3) OR presence of a central venous catheter
(days 1–3) AND at least TWO of the following—total parenteral nutrition (days 1–3), any dialysis (days 1–3), any major surgery
(days −7–0), pancreatitis (days −7–0), any use of steroids (days −7–3), or use of other immunosuppressive agents (days −7–0).
The rate of invasive candidiasis among patients meeting the rule was 9.9%, capturing 34% of cases in the units, with the following
performance: relative risk 4.36, sensitivity 0.34, specificity 0.90, positive predictive value 0.01, and negative predictive
value 0.97. The rule may identify patients at high risk of invasive candidiasis.
Results of this project were partially presented at Focus on Fungal Infections 14, New Orleans, LA, USA, 2004. Abstract no.
51. 相似文献
3.
A. D. Kirk W. S. Cherikh M. Ring G. Burke D. Kaufman S. J. Knechtle S. Potdar R. Shapiro V. R. Dharnidharka H. M. Kauffman 《American journal of transplantation》2007,7(11):2619-2625
Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk. 相似文献
4.
Nelson Wolosker Guilherme Yazbek José Ribas Milanez de Campos Paulo Kauffman Augusto Ishy Pedro Puech-Leão 《Clinical autonomic research》2007,17(3):172-176
Background Sympathectomy is the treatment of choice for primary hyperhidrosis. One curious occurrence that is difficult to explain from
an anatomophysiological point of view in cases of video-assisted thoracoscopic sympathectomy (VATS) for the treatment of palmar
hyperhidrosis (PH) is the observed improvement in plantar hyperhidrosis (PLH). Nevertheless, current reports on VATS rarely
describe the effect on PLH or just give superficial data. The aim of this study was to prospectively investigate, how surgery
affects PLH in patients with PH and PLH over one-year period.
Methods From May 2003 to January 2004, 70 consecutive patients with combined PH and PLH underwent VATS at the T2, T3, or T4 ganglion
level (47 women and 23 men, with mean age of 23 years).
Results Immediately after the operation, all the patients said they were free from PH episodes, except for two patients (2.8%) who
suffered from continued PH. Compensatory hyperhidrosis (CH) of various degrees was observed in 58 (90.6%) patients after one
year. Only 13 (20.3%) suffered from severe CH. There was a great initial improvement in PLH in 50% of the cases, followed
by progressive regression, such that only 23.4% still presented that improvement after one year. The number of cases without
overall improvement increased progressively (from 17.1% to 37.5%) and the numbers with slight improvement remained stable
(32.9–39.1%). Of the 24 patients with no improvement after one year, 6 patients graded plantar sweating worse.
Conclusion Patients with PH and PLH who undergo VATS to treat their PH present a good initial improvement in PLH that reduces to a lower
level of improvement after the one-year period. 相似文献
5.
Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation 总被引:5,自引:0,他引:5
Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs. 相似文献
6.
S E Irwin G Y Kwei G R Blackburn R Thurman F C Kauffman 《Environmental and molecular mutagenesis》1992,19(3):253-258
Comparison of the mutagenicity of nine isomeric benzo(a)pyrenyl [B(a)P] phenols conjugated with either sulfate or glucuronide was carried out using strain Salmonella typhimurium TA98. Of the nine conjugates tested, only B(a)P-1-sulfate was mutagenic. Accordingly, the mutagenicity of B(a)P-1-sulfate was compared with that of B(a)P and 1-hydroxybenzo(a)pyrene [B(a)P-1-OH] in the presence and absence of rat lung S9 and Aroclor-induced liver S9 with and without an NADPH-generating system. B(a)P-1-sulfate was slightly mutagenic, whereas B(a)P and the 1-hydroxy derivative were nonmutagenic when S9 fractions and NADPH were omitted. Addition of induced liver S9 with NADPH caused mutagenicity with B(a) -1-OH greater than B(a)P greater than B(a)P-1-sulfate. B(a)P-1-sulfate was the only mutagenic species when lung S9 was added. This mutagenicity did not require NADPH. Sodium sulfite, an inhibitor of arylsulfatase, decreased the mutagenicity of B(a)P-1-sulfate. These data suggest that a unique mutagenic species is generated from B(a)P-1-sulfate via arylsulfatase in rat lung. 相似文献
7.
8.
Long-chain fatty acids inhibit glucuronidation of benzo(a)pyrene phenols in perfused liver; therefore, this study was designed to investigate interactions of fatty acids with beta-glucuronidase, glucuronosyl transferase, and energy supply. In beta-glucuronidase-deficient C3H/He mice, infusion of oleate (250 microM) increased the release of free benzo(a)pyrene phenols from 14 to 33 nmol/g/h and decreased release of glucuronides into the perfusate from 25 to 17 nmol/g/h. Rates of accumulation of glucuronides in the liver were also diminished from 11 to 4 nmol/g/h after infusion of oleate (250 microM). Fatty acids did not affect the release of benzo(a)pyrene metabolites into bile, and the ratio of free phenol to glucuronide production was increased from 0.57 to 1.30. A similar trend was observed in livers from DBA/2 mice that have beta-glucuronidase. Rates of hydrolysis of benzo(a)pyrene-O-glucuronide were not altered in isolated microsomes by addition of oleoyl coenzyme A (CoA) or octanoyl CoA (10- approximately 100 microM). Thus, we conclude that fatty acids do not alter glucuronidation by acting on beta-glucuronidase. The concentration of cofactors (UDP-glucuronic acid, UDP-glucose, and adenine nucleotides) involved in hepatic conjugation was not altered by infusion of concentrations of oleate (300 microM) that inhibited glucuronidation in perfused livers. When oleate concentrations were increased to 600 microM, UDP-glucuronic acid and UDP-glucose decreased 44 and 49%, respectively, and the ATP:ADP ratio declined concomitantly. Oleoyl CoA inhibited UDP-glucuronosyl transferase noncompetitively (half-maximal inhibition, 10 microM) in microsomes with 3-hydroxy-benzo(a)pyrene or p-nitrophenol as substrate. In contrast, octanoyl CoA was a very poor inhibitor of transferase activity. Inhibition of the transferase by oleoyl CoA was increased markedly by treatment with detergents (Triton X-100), i.e., half-inhibition of glucuronosyl transferase was obtained with about 2 microM oleoyl CoA. Inhibition of UDP-glucuronosyl transferase by oleoyl CoA was also increased in a dose-dependent manner by albumin, possibly due to increasing access of the CoA derivative to the enzyme. Collectively, these data indicate that fatty acids diminish glucuronidation via the formation of acyl CoA compounds that inhibit UDP-glucuronosyl transferase noncompetitively. 相似文献
9.
Benzo(a)pyrene 7,8-dihydrodiol-9,10-epoxide (BPDE), accepted as the ultimate carcinogen of benzo(a)pyrene, has a very short half-life in aqueous solutions yet induces lung tumors when injected into infant mice. To evaluate the possibility that metabolites of BPDE, principally in the form of stable conjugates, contribute to binding to DNA in peripheral tissues, infant mice were injected i.p. with 39 nmol (+/- ) anti-BPDE. One h after injection, 5% of the dose was recovered in serum and appeared mostly as conjugated metabolites (54% as glucuronides and 16% as glutathione conjugates). Amounts of direct acting electrophiles in serum estimated by trapping with DNA comprised less than 0.02% of the injected dose. No more than 10% of the radioactivity in extracts of liver, lung, and kidney was recovered as BPDE. Glutathione conjugates predominated in the liver and lung, whereas glucuronides were the major metabolites in kidney. Radioactivity bound to DNA in liver, lung, and kidney was 21.5, 42.7, and 7.8 pmol/mg, respectively. Despite the rapid conversion of BPDE to stable conjugates, 32P-postlabeling profiles of DNA adducts in lung closely resembled that noted after addition of BPDE directly to lung homogenate. Thus, the reactive intermediate as well as stable conjugates of BPDE may be transported to target tissues where they initiate tumors. 相似文献
10.